The information provided herein and references cited are provided solely to assist the understanding of the reader, and does not constitute an admission that any of the references or information is prior art to the present invention.
Membrane-spanning proteins such as G Protein Coupled Receptors (GPCRs) are among the most important classes of drug targets, currently targeted by about 30% of therapeutics in the market. However, the use of GPCRs for basic drug discovery and development in the pharmaceutical industry is inherently difficult due to the notoriously low expression, homogeneity, and stability thereof, and the high conformational flexibility of these integral membrane proteins, especially when removed from the cellular environment. This has greatly limited the success of protein-based approaches such as small molecule screening/assays and structural determination for structure-guided drug discovery, as well as antibody discovery efforts. These limitations remain to be addressed.
Importantly, only a very limited number of therapeutic antibodies targeting GPCRs have been approved, while most marketed therapeutics are small molecules or small peptides. As experienced often with non-GPCR targets, biologic drugs such as antibodies may enable access to a therapeutic space where small molecule drugs have failed. Therefore, the availability of GPCR-targeting antibodies will potentially facilitate previously unattainable opportunities for the betterment of human health.